Design and Synthesis of Novel Apoptosis Inducer as Anticancer Agents

Abstract

Cancer is one of the lethal diseases in the world leads to death when diagnosed at the later stage. There are many types of cancers such as lung, blood, breast, skin, etc. which are induced in the human body due to certain carcinogens and many other reasons. Preventive measures for protection from cancer include avoiding smoking, chewing tobacco, exposure to the chemicals, etc. Skin cancer is one of the cancers which occurs due to the exposure to UV radiation and can lead to very dangerous effects in the normal healthy body. 3D-QSAR was carried on 26, benzothiazole derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested that by substituting hydrophobic, bulky and electronegative group potency of the compound can be increased. According to contour map description, design various carbocyclic and heterocyclic derivate and design synthetic route and Synthesis of 10 carbocyclic and heterocyclic derivatives were carried out and spectral characterization was carried out using Mass, 1H-NMR and 13C-NMR spectroscopy. Pharmacophore model was generated using 10 structurally diverse molecules using DISCOtech refined with GASP module of Sybyl. Out of obtained four refined models, model_2 containing four features; two donor sites, two acceptor atom, and three hydrophobic regions had highest fitness score and best validation results. Hence best model, model_2 was used as a query for virtual screening in NCI database and IBS database and 10 compounds with Qfit value ≥90 were retrieved in the individual database. The quinoline ring which is bio-isostere ring retrieved as a hit in virtual screening was selected as core moiety. Synthesis of top 10 quinoline derivatives was carried out and spectral characterization was carried out using Mass, 1H-NMR and 13C-NMR spectroscopy..